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Biomedical subjects

W Wong

Publications and source records attributed to W Wong.

At least 73 records · Page 4Linked to original sources

Massive subdural haematoma: an unusual complication of septicaemia in preterm very low birthweight infants.

Non-traumatic massive subdural haematoma is a rare condition in newborn infants and is usually associated with hereditary coagulation disorders or congenital vascular malformation. Its occurrence in preterm very low birthweight infants secondary to systemic bacterial infection has not been reported. We describe two extremely preterm neonates who developed massive subdural haematoma as a result of gram-negative septicaemia and disseminated intravascular coagulation. Both infants suffered severe parenchymal cerebral injury and hydrocephalus. Clinicians should be aware of this unusual and catastrophic complication if a very low birthweight infant with severe sepsis and disseminated intravascular coagulation suddenly deteriorates despite successful treatment with antibiotics. Radiological imaging by cranial ultrasound or computed tomography scanning should be routinely considered in all such infants for the detection of intracranial bleeding.

Bacteremia↗

Paediatric nephrotic syndrome in Auckland, New Zealand.

OBJECTIVE: To review children with nephrotic syndrome in Auckland, New Zealand. METHODS: All children admitted to Auckland Children's Hospital between January 1984 and December 1994 with nephrotic syndrome and a renal biopsy had their charts retrospectively reviewed and the appropriate information summarised. RESULTS: Fifty-seven children biopsied with nephrotic syndrome were available for review. The mean age at diagnosis was 5.4 years, standard deviation (SD) 3.9 years, with mean follow-up of 5.7 years. The histologies of the renal biopsies were: minimal change nephrotic syndrome (MCNS) in 37%, focal segmental glomerulosclerosis in 19%, membranoproliferative glomerulonephritis (MPGN) in 23% and other causes in 21%. Maori children were most likely to have MPGN. Steroid resistance was present in 66% of children. End stage renal failure developed in 26% of patients and chronic renal failure in 4% of patients. CONCLUSION: In this series the proportion of children with MCNS is low and significant numbers of children with nephrotic syndrome progressed to chronic renal failure and end stage renal failure.

Adolescent↗

Cognitive task analyses for decision centred design and training.

This paper presents three case studies of Cognitive Task Analysis (CTA) for defining systems design and training requirements. The approach taken involves a modification of the critical decision method of Klein et al. The authors utilized the revised CDM to obtain information from expert white-water rafting guides, general aviation pilots, and emergency ambulance dispatchers. The information obtained was used to develop multi-media tools for training rafting guides and general aviation pilots, and to redesign the VDU display requirements for the ambulance dispatchers. The examples demonstrate the utility of an approach to CTA that is closely based on relevant theory, and provides guidance to practitioners wishing to apply CTA techniques.

Adolescent↗

Clinical prediction of post-extubation radiological changes of the chest in newborn infants.

OBJECTIVE: Whether a chest radiograph should be performed routinely in all infants after extubation, or selectively only in those with clinical deterioration, is a controversy in neonatal unit practice. This study tested the hypothesis that most cases of post-extubation radiological deterioration in the lungs could be detected by clinical assessment. METHODS: A chest radiograph was performed at 8 h post-extubation in 100 episodes of extubation in 85 newborn infants ventilated for a variety of lung diseases. Each infant was assessed at the same time by a neonatologist blinded to the radiological findings, to determine whether a chest radiograph would have been requested based on clinical judgement. The infants were continuously monitored for their respiratory and oxygenation status before and after extubation. RESULTS: Compared to the pre-extubation chest radiographs, 23 of the 100 post-extubation chest radiographs showed either deterioration of the pre-existing lung pathologies or appearance of significant new pathologies. The clinicians' assessment failed to detect most of the deterioration, with a sensitivity of only 21.7%. Systematic analysis of the infants' clinical parameters showed that the development of significant intercostal/subcostal retraction, and an increase in inspired oxygen concentration by > or = 7% after extubation, were the best predictors of post-extubation radiological deterioration (sensitivity 82.6%, specificity 62.3%, positive predictive value 39.6%, and negative predictive value 92.3%). Serial blood gas in contrast had little predictive value. CONCLUSION: We conclude that most cases of radiological deterioration of the lungs after extubation are clinically predictable, provided the correct clinical criteria are used.

Blood Gas Analysis↗

Is homozygous alpha-thalassaemia a lethal condition in the 1990s?

Two cases of homozygous alpha-thalassaemia who received active treatment in accordance with parental wishes are reported. One infant survived and the other, although successfully weaned off mechanical respiratory support, unexpectedly developed portal vein thrombosis and died. Homozygous alpha-thalassaemia, a condition previously considered to be universally fatal, and an indication for therapeutic abortion, is now potentially curable with advances in diagnostic technology and treatment. However, active management of these cases raises serious ethical questions and has major financial implications on the health-care system. Invasive prenatal and intensive postnatal interventions should remain experimental and cannot be recommended as routine clinical practice until the questions of long-term neurodevelopmental outcome, and the morbidity and mortality associated with bone-marrow transplantation have been fully addressed. As a result of advances in information technology, more and more parents of affected foetuses are likely to request active treatment.

Fatal Outcome↗

Risk factors for Enterobacter septicemia in a neonatal unit: case-control study.

Thirty cases of Enterobacter aerogenes or Enterobacter cloacae septicemia diagnosed over a 32-month period in a tertiary care neonatal unit were enrolled in a case-control study. Each case patient was matched with two controls (patients occupying the cots nearest the case patient when the latter developed septicemia). Of the 32 perinatal characteristics evaluated, 11 were identified by univariate analysis to be significantly associated with the infection. These included parents being residents of the Vietnamese refugee camps, respiratory distress syndrome, necrotizing enterocolitis, umbilical arterial catheterization, umbilical venous catheterization, bladder catheterization, mechanical ventilation, antibiotic treatment, peripheral venous catheterization, nasogastric intubation, and parenteral nutrition. Multivariate analysis, however, showed that preceding bladder catheterization and ongoing parenteral nutrition were the only independent risk factors for enterobacter septicemia. Strict aseptic technique in the preparation of parenteral nutrition fluid and avoidance of bladder catheterization are measures that may reduce the risk of enterobacter sepsis for newborns.

Bacteremia↗

CMV infection is associated with transplant renal artery stenosis.

Transplant renal artery stenosis (TRAS) is a significant cause of graft dysfunction, with no clearly defined aetiology. Evidence suggests a role for cytomegalovirus (CMV) infection in cardiac transplant vasculopathy and in native coronary artery restenosis after angioplasty. We investigated the relationship between CMV infection after renal transplantation and subsequent development of TRAS. Of 917 patients receiving renal transplants at a single centre from 1978 to 1994, 75 had TRAS diagnosed by angiography. Each was paired with a control transplanted patient with no TRAS, matched for age, sex, year of transplant and number of grafts. Incidence of CMV infection between transplantation and the time of diagnosis of TRAS was assessed in both groups, using clinical and serological criteria to assign patients to three groups: definite CMV infection (CMV-DEF), possible infection (CMV-POSS) and no evidence of infection (CMV-NUL). CMV-DEF was significantly more common in TRAS than in controls (36 vs. 12, respectively, p < 0.001) and CMV-NUL was less common (TRAS 15, controls 33). We have previously reported an increased incidence of acute rejection in patients with TRAS. The subset of patients with no rejection episodes also had significantly more CMV-DEF cases in the TRAS group (54%) than in controls (10%) (p = 0.002). The data are consistent with the hypothesis that CMV infection can contribute to the development of TRAS. The relationship between CMV and TRAS did not arise from an excess of anti-rejection treatment in the TRAS group. CMV-induced large-vessel damage in immunosuppressed patients may occur through local infection and the mitogenic actions of viral gene products within cells of the vessel wall.

Adult↗

Streptozotocin- and alloxan-induced diabetes modifies total plasma and lipoprotein lipid concentration and composition without altering cholesteryl ester transfer activity.

The objectives of this study were to determine the total plasma and lipoprotein lipid concentration and composition and cholesteryl ester transfer activity in two diabetic animal models (alloxan-induced diabetes in rabbits and streptozotocin-induced diabetes in rats). Furthermore, we wanted to determine if the severity of diabetes influences lipoprotein lipid profiles and cholesteryl ester transfer activity. Rats and rabbits were randomly divided into non-diabetic and diabetic groups. Rats were administered either 55 mg/kg or 100 mg/kg of streptozotocin intravenously through the tail vein, while rabbits were administered 100 mg/kg or 200 mg/kg of alloxan intravenously through the marginal ear vein under light anesthesia. Hyperglycaemia was tested for at 48 hr following the doses. Total and lipoprotein cholesterol and triglyceride concentrations using enzymatic kits and cholesteryl ester transfer activity from low-density lipoproteins to high-density lipoproteins using 3H-cholesteryl ester incorporated into low-density lipoproteins were determined. Elevations in both total and lipoprotein cholesterol and triglyceride concentrations and alterations in lipoprotein lipid composition are observed following the onset of drug-induced diabetes in rats and rabbits compared to non-diabetics. However, these findings were observed only in animals administered the higher streptozotocin and alloxan dose. Furthermore, cholesteryl ester transfer from low-density lipoproteins to high-density lipoproteins is not significantly different in drug-induced diabetic compared to non-diabetic rats and rabbits, regardless of which streptozotocin and alloxan dose was used. These findings suggest that difference in lipoprotein lipid concentration and composition as a result of drug-induced diabetes is independent of cholesteryl ester transfer activity in both rats and rabbits. Furthermore, diabetic severity may influence lipoprotein metabolism in these animal models.

Alloxan↗

Differences in the lipoprotein distribution of free and liposome-associated all-trans-retinoic acid in human, dog, and rat plasma are due to variations in lipoprotein lipid and protein content.

The objective of the proposed study was to determine the distribution in plasma lipoprotein of free all-trans retinoic acid (ATRA) and liposomal ATRA (Atragen; composed of dimyristoyl phosphatidylcholine and soybean oil) following incubation in human, rat, and dog plasma. When ATRA and Atragen at concentrations of 1, 5, 10, and 25 micrograms/ml were incubated in human and rat plasma for 5, 60, and 180 min, the majority of the tretinoin was recovered in the lipoprotein-deficient plasma fraction. However, when ATRA and Afragen were incubated in dog plasma, the majority of the tretinoin (> 40%) was recovered in the high-density lipoprotein (HDL) fraction. No differences in the plasma distribution between ATRA and Atragen were found. These data suggest that a significant percentage of tretinoin associates with plasma lipoproteins (primarily the HDL fraction) upon incubation in human, dog, and rat plasma. Differences between the lipoprotein lipid and protein profiles in human plasma and in dog and rat plasma influenced the plasma distribution of ATRA and Atragen. Differences in lipoprotein distribution between ATRA and Atragen were not observed, suggesting that the drug's distribution in plasma in not influenced by its incorporation into these liposomes.

Animals↗

Randomised crossover trial of salbutamol aerosol delivered by metered dose inhaler, jet nebuliser, and ultrasonic nebuliser in chronic lung disease.

AIMS: To compare the efficacy of salbutamol delivered by metered dose inhaler (MDI), jet nebuliser, and ultrasonic nebuliser in ventilated infants with chronic lung disease. METHODS: Twenty preterm ventilated infants with chronic lung disease were enrolled in two studies. In study 1 (n = 10), each infant was given 200 micrograms of salbutamol at 4 hour intervals and in random sequence from a metered dose inhaler-spacer device, a jet nebuliser, and an ultrasonic nebuliser with a small medication cup. The infants were monitored for heart rate, transcutaneous pO2, pCO2, and oxygen saturation, respiratory system resistance and compliance before and after each treatment. Infants in study 2 (n = 10) were similarly studied except for the use of a different jet nebuliser. RESULTS: The mean (SEM) maximum percentage decreases in respiratory system resistance, observed at 30 minutes after aerosol delivery were study 1: MDI: 44.3 (4.3)%; jet: 32.3 (3.4)%; ultrasonic: 56.1 (3.2)%; study 2: MDI: 28.6 (1.0)%; jet: 16.9 (1.4)%; ultrasonic: 42.1 (1.6)%. During the first hour after treatment, a significantly faster heart rate and higher transcutaneous pO2 were associated with the use of the ultrasonic nebuliser or MDI than with the jet nebulisers in both studies. The use of the ultrasonic nebuliser but not the other devices also resulted in a lower transcutaneous pCO2 and improved respiratory system compliance in study 2. CONCLUSIONS: These findings suggest that among the devices tested, the delivery of salbutamol aerosol to the lower respiratory tract was greatest using the ultrasonic nebuliser, and least with the jet nebulisers.

Administration, Intranasal↗

Double blind, randomised, placebo controlled study of oral vancomycin in prevention of necrotising enterocolitis in preterm, very low birthweight infants.

AIMS: To evaluate the effectiveness of oral vancomycin in the prophylaxis of necrotising enterocolitis in preterm, very low birthweight infants. METHODS: A prospective, double blind, randomised, placebo controlled study in a tertiary referral centre of a university teaching hospital was conducted on 140 very low birthweight infants consecutively admitted to the neonatal unit. The babies were randomly allocated to receive oral vancomycin (15 mg/kg every 8 hours for 7 days) or an equivalent volume of placebo solution. Prophylaxis was started 24 hours before the start of oral feeds. All suspected cases of necrotising enterocolitis were investigated with a full sepsis screen and serial abdominal radiographs. Necrotising enterocolitis was diagnosed and staged according to modified Bell's criteria. RESULTS: Nine of 71 infants receiving oral vancomycin and 19 of 69 infants receiving the placebo solution developed necrotising enterocolitis (p = 0.035). Infants with necrotising enterocolitis were associated with a significant increase in mortality (p = 0.026) and longer duration of hospital stay (p = 0.002). CONCLUSIONS: Prophylactic oral vancomycin conferred protection against necrotising enterocolitis in preterm, very low birthweight infants and was associated with a 50% reduction in the incidence. However, widespread implementation of this preventive measure is not recommended, as it would only be effective in necrotising enterocolitis caused by Gram positive organisms and could increase the danger of the emergence of vancomycin resistant or dependent organisms. Its use should be restricted to a high prevalence nursery for a short and well defined period in a selected group of high risk patients.

Administration, Oral↗

Phase I trial of retinoic acid and cis-platinum for advanced squamous cell cancer of the head and neck based on experimental evidence of drug synergism.

OBJECTIVE: Cis-platinum and 13-cis-retinoic acid have received much attention in the treatment of head and neck squamous cell cancer. Even though they have different mechanisms of action, little information is available on their interaction. This paper reviews experimental evidence for retinoic acid-cis-platinum synergy and presents toxicity data from patients with stage IV head and neck squamous cell cancer participating in a phase I trial combining 13-cis-retinoic acid and cis-platinum. METHODS: Patients were given 13-cis-retinoic acid orally daily for 7 days before and daily during high-dose (150 mg/m2 per week for 4 weeks) intraarterial cis-platinum treatment with concurrent radiation. Toxicity was scored with use of the cancer and leukemia group B scale. RESULTS: In the phase I clinical trial, 15 patients were treated to determine a maximum tolerated dosage for 13-cis-retinoic acid of 20 mg/day. Grade 4 hematologic toxicity was dose limiting in 3 of 8 patients treated with 40 mg/day and in 1 patient treated with 60 mg/day. There were no deaths caused by toxicity; 12 of the 15 patients received all four weekly doses and the remaining 3 received three doses. Of 10 patients with fully evaluable data, all achieved a complete response at the primary site and 9 had a complete response in the neck. One patient had persistent neck disease after chemoradiation, and this tumor was removed with neck dissection. CONCLUSIONS: 13-Cis-retinoic acid and cis-platinum are strongly synergistic against head and neck squamous cell cancer in vitro. Pretreatment with retinoic acid results in stronger synergy than concurrent drug exposure alone. Preliminary clinical experience with combined retinoic acid and cis-platinum in a design that parallels the in vitro study indicates that toxicity is acceptable with 13-cis-retinoic acid dosages of 20 mg/day in a high-dose-intensity intraarterial chemoradiation regimen.

Administration, Oral↗

Delivery of salbutamol to nonventilated preterm infants by metered-dose inhaler, jet nebulizer, and ultrasonic nebulizer.

To identify the most efficient device for the delivery of bronchodilator aerosol to nonventilated preterm infants with chronic lung disease, we compared the metered dose inhaler (MDI) used in conjunction with a non-valved spacer, an ultrasonic nebulizer with a small medication cup, and two jet nebulizers. The subjects were enrolled in two double-blind randomized crossover studies. In study A (n=10), each infant was given a nominal dose of 200 microg of salbutamol by a MDI (Ventolin) at 4 h intervals, and in random sequence via an Aerochamber (Neonatal Aerochamber) with its one-way valve removed, an ultrasonic nebulizer with a small cone-shaped medication cup (Siemens Electronics), and a jet nebulizer (Side-stream). Their functional residual capacity (FRC) and static respiratory system mechanics were measured before, and at 15, 30, 60, and 120 min after aerosol delivery. Study B (n=10) was carried out in an identical manner, but with a different jet nebulizer (Hudson). In both studies, administration of salbutamol aerosol via the MDI Aerochamber or ultrasonic nebulizer resulted in a significantly greater reduction in respiratory system resistance than via jet nebulizers. Furthermore, the use of MDI Aerochamber or ultrasonic nebulizer was associated with a greater degree of post-treatment tachycardia and improvement in FRC. The bronchodilating effect of salbutamol delivered via the ultrasonic nebulizer appeared to be slightly greater than that via the MDI-Aerochamber, receiving significance only in Study B. We conclude that both the metered-dose inhaler used with a nonvalved Aerochamber and the ultrasonic nebulizer with a small medication cup are both more efficient than the jet nebulizers in preterm infants.

Albuterol↗

Lipid transfer protein I facilitated transfer of cyclosporine from low- to high-density lipoproteins is only partially dependent on its cholesteryl ester transfer activity.

The purpose of this study was to determine if lipid transfer protein (LTP I) regulates the plasma lipoprotein distribution of cyclosporine (CSA). Experimental strategies that involved the supplementation and inhibition of LTP I were used to test these hypotheses. Incubation of CSA with human plasma supplemented with exogenous LTP I resulted in a significantly greater percentage of CSA recovered in the high-density lipoprotein (HDL)/lipoprotein deficient plasma (LPDP) fraction than in the low-density lipoprotein (LDL)/very low-density lipoprotein (VLDL) fraction compared to plasma which had no exogenous LTP I added. Incubation of radiolabeled cholesteryl ester (CE) or CSA-enriched HDL or LDL in T150 buffer supplemented with LTP I resulted in a significantly greater percentage of CE than CSA being transferred from HDL to LDL and LDL to HDL. However, the percent transfer from LDL to HDL was significantly lower for CE than CSA when these particles were incubated in LPDP that contained endogenous LTP I. The percent transfer of CE from HDL to LDL and LDL to HDL was significantly decreased in the presence of TP2, a monoclonal antibody directed against LTP I, compared to controls. The percent transfer of CSA from LDL to HDL was significantly decreased in the presence of TP2. However, the percent transfer of CSA from HDL to LDL in the presence of TP2 was not significantly different compared to controls. These findings suggest that the transfer of CSA between HDL and LDL is only partially facilitated through LTP I CE transfer activity.

Carrier Proteins↗

A mercuric ion uptake role for the integral inner membrane protein, MerC, involved in bacterial mercuric ion resistance.

Bacterial detoxification of mercuric ion depends on the presence of one or more integral membrane proteins (MerT and/or MerC) whose postulated function is in transport of Hg2+ from a periplasmic Hg2+-binding protein (MerP) to cytoplasmic mercuric reductase. In this study, MerC from the Tn21-encoded mer operon was overexpressed and studied in vesicles and in purified form to clarify the role played by this protein in mercuric ion resistance. MerC-containing vesicles were found to take up mercuric ion independently of MerP. Since uptake correlated with the level of MerC expression was unaffected by osmotic pressure, and was only partially decreased in the presence of 0.05% Triton X-100, the observed uptake appears to represent mainly binding to MerC. Binding was inhibited by thiol-specific reagents, consistent with an essential role for cysteine residues. The essential thiol groups were inaccessible to hydrophilic thiol reagents, whereas hydrophobic reagents completely abolished Hg2+ binding. These observations are consistent with the predicted topology of the protein, wherein all 4 cysteine residues are either in the cytoplasm or the bilayer. A role for MerC in Hg2+ transport is thus also likely. Based on these results, a modified model for bacterial Hg2+ transport is proposed.

Bacterial Proteins↗

Resting B cells as tolerogens in vivo but only for minor histocompatibility antigens: evidence for activation of resting B cells in vivo.

BACKGROUND: Small, resting B cells (rB cells) express major histocompatibility complex (MHC) class II molecules but not the putative costimulatory molecules, B7-1 (CD80) and B7-2 (CD86); they are classified as nonprofessional antigen-presenting cells. rB cells have been shown to be capable of anergizing T cells in vitro and inducing the prolonged survival of skin grafts mismatched for a single minor histocompatibility (miH) antigen, H-Y. The aim of this study was to investigate ability of rB cells to induce unresponsiveness to multiple miH and MHC antigens. METHODS: Mice were pretreated with 1 x 10(7) donor rB cells 14 days before transplantation of cardiac grafts mismatched for either a single or multiple miH and/or MHC antigens in vivo. RESULTS: rB cells induced indefinite prolongation of cardiac grafts mismatched for H-Y antigen (C57BL/10 male to female). Moreover, 50% of grafts mismatched for multiple miH antigens (C3H to CBA) were accepted indefinitely in recipients treated with donor rB cells. In marked contrast, when grafts were mismatched for either a single MHC class I antigen, Kb (CBK to CBA), or multiple MHC and miH antigens (C57BL/10 to C3H), pretreatment with rB cells did not prolong graft survival. To investigate why rB cells were ineffective tolerogens for grafts mismatched for MHC antigens, we examined the fate of the cells in vivo. We demonstrate that, after intravenous injection of rB cells, expression of B7-2 was induced within 24 hr. CONCLUSIONS: These data suggest that rB cells may be less effective at inducing specific unresponsiveness to MHC antigens because of their rapid activation in vivo.

Animals↗